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Thursday, February 5, 2015

Editorial on HCC biopsy in Hepatology

Dear Laennec friends,

Please see the Hepatology-Editorial (click here or image), Mike and I fought through regarding the HCC biopsy issue (for the cost of an anti-editorial from Jordi Bruix and Morris Sherman). Any kind of support, for example letter to the editor, more/new arguments, or local activities are certainly very helpful and appreciated. Maybe we could also discuss the issue at the next Laennec meeting again? Best wishes

as promised, I have collected the comments that have reached me regarding the editorial and have tried to sort them (see attached). It may also be used as a starting point for our discussion in Paris – thus I would also like to hand it over to Valerie by this. Mike and I would certainly be very happy if this discussion evolves further for the aim of getting HCC biopsy and fostering the position of liver pathology. Best wishes

I read both editorials and it was a fascinating discussion from both sides. It is indeed an important issue. However, I completely agree with Mike and Peter that we should push for these biopsies. I am in agreement that the Laennec Society as a group can come up with a letter to the editor of Hepatology supporting this concept.

I wholeheartedly support Venancio’s proposal to cull cases from our individual institutions and come up with a consensus statement based on these experiences.

Dear all,I think that Mike and Peter wrote an excellent editorial. For cancer of the lung, breast and colon even prostate it is a routine nowadays to make molecular classification for better treatment and I don't understand why this is not possible for HCC's. We need the tissue to make a complete diagnosis for the personalized treatment there is no alternative from serum or blood or radiology. It is an important issue but there is still a long way to go.BestHans

Dear All:I agree w/Hans, Isabel, and Venancio, and I suspect anyone who reads the article. Beautifully written article that covered so many very important points. This is an opinion that Peter has been making for quite some time, and I tried to express when I was AE of HEPATOLOGY after an ILCA meeting that was full of presentations particularly short on tissue acquisition studies; Greg Gores even joined me in the editorial. Why liver not only remains the only solid organ that does not require a tissue dx prior to treatment, and continues to rely on imaging studies that we all know are great, getting better but are NOT always correct, is absolutely incredible. Anyone who does explant pathology has experienced the "oops" there were several more HCC's that the imagers saw….or "oops" you TACE'd a DN or CN or no, that wasn't HCC, it was a mixed hepatobiliary/biphenotypic primary liver carcinoma….don't they want to know prior to treatment?And how will the field of treatment ever advance? And how do we teach our next generations of pathologists?

And yet, when molecular studies are reported, the scientists seem so surprised at the results of tumor heterogeneity! What we morphologists have been trying to say for years. So surprised that an "HCC" could have "biliary" features…another concept that's been quite hard to get acceptance…

Do we just keep banging our heads against the wall? Do we get the imaging folks to join in? Can we possibly get some of the major surgeons to join us? Could we possibly get oncologists to require tissue prior to treatment?

Hope to see folks in Boston; don't know if I'm going to be able to make Laennec.Thanks again for a terrific piece, and congratulations, Mike and Peter.

Dear all, As many have already noted, this is an outstanding contribution and should influence many. All of the suggestions, including that of Venancio to carry out a study to support the paper, are excellent. An additional suggestion: obtain permission from Hepatology (should not be difficult) and submit the exact same material to leading oncology journals (e.g. Cancer, Journal of Clinical Oncology, etc) which are read by oncologists who may be involved with HCC patients but do not necessarily read Hepatology. See you all in Paris. Best wishes. Stephen

I think that we all agree that it is becoming evident that primary liver cancers are more heterogeneous mix of cancer clones more than we previously thought. We can classify or reclassify HCC as we want, but in reality we can’t convince the community with the necessity of sampling the tumors unless we identify precise key druggable targets that can block as many mutated/altered signaling pathways as possible. Perhaps WE are lacking sufficient preclinical studies on liver cancers /studies on PDX, pharma collaboration etc

Wonderful ideas from many centers. I agree with Dr. Geller that the medical oncologists have a very strong influence on this process. The last 10 years of my medical career were spent as medical director of a community hospital oncology program and as such I directed the local medical CME conferences for the all oncologists (medical and radiation), and ran all the conferences including presenting the histopathology. It is clear that the medical oncologists call the process of diagnosis in the general medical community, perhaps not at the academic centers. The GI doctors in my private practice lost all interest in the patient once HCC was considered. They had no role to play. So it is essential that this message about the essential importance of the liver biopsy of HCC be carried to and by the medical oncologists (in the communities where most of the HCC is actually recognized). There are a few academic medical oncologists directly involved with HCC primarily but they are a rare species. These medical oncologists should be counseled regarding our project (like Dr. Alan Venook UCSF and others, many known to Mike Torbenson). I look forward to this message being successfully broadcast to the key players. (not just pathologists). john craig (retired in Carmel).

thank you to all of you for the great support, helpful comments and enthusiasm!! It is great to see how good and creative our Laennec network is working! This is a true bottom-up activity and very encouraging! Let me suggest the following: I will wait until the end of the week (for potential further ideas), then summarize all these helpful aspects into a single piece of paper and then ask all of you how distribute these activities; this is very important that many of you take part and join in, as Mike and myself are certainly seen as biased and ‘burned’. With this agenda I will also ask Valerie and Pierre to give us a little spot in the Paris program to briefly discuss progress and further activities. Thank you again already to all of you. Best wishes

What great ideas! In the end, it seems to me that the pathway most likely to be successful has to be paved with peer reviewed and published data that demonstrates the value of liver biopsies in improving patient care. I fully agree that this data has to be presented/published in the meetings/journals read by oncologist, in addition to the GI clinical groups. As a society and as individuals, I’m sure we can come up with a number of great project ideas to do this, such as the one outlined by Venancio. And I look forward to discussing this more in Paris!

The literature to date has been unevenly sided, with strong advocacy against biopsy. This in part reflects advances in medicine, but also reflects the relative silence from the pathology community. We can change this. As we do so, I suppose it is only natural that there will be negative reactions by those who have advocated against biopsies (see for example the opposing editorial). But I think it is worth the effort.

Thank you for sharing this beautiful paper, congratulations, Mike and Peter.I agree with the idea that we have better to discuss this issue with oncologists as well as hepatologists.Although APASL guidline is similar to AASLD and EASL guideline about liver biopsy, I found that liver biopsy issue is more supported by oncologist during last APPLE (Asia-Pacific Primary Liver Cancer Expert Meeting).I am looking forward to discus this issue further in Laennec meeting , 2015.See you in Paris.

hey all - sorry for my delay in chiming in and i haven't reaaly caught up wth every bit of this thread - been dealing with some family stuff in florida (i LOATHE florida (but my mom is fine in case "family stuff" worried you ))

i agree with all the suggestions so far.

but i'm also thinking that this is really interesting from the standpoint that their position is based on their understanding of the radiologists' position - BUT it seems to me that the radiology position is becoming ever more nuanced and complex.

since we have a couple of radiologists in the group, perhaps we could encourage a response from them....? or maybe alex could motivate the Li-RADS group as a whole to write a response...?

could be another solid way to chip away if not actually undermine the standard view.

I have been thinking about how many core biopsies one can feasibly perform on a patient with a sizeable tumor (esp in a cirrhotic background with likely PT derangements) to get a decent appraisal of the various heterogeneous components for planning personalized molecular targeted therapy.

Have always been advocating the resurrection of fine needle aspiration/ biopsy for more representative sampling and accessibility.

FNA has its limitations and issues no doubt. But has a role to play esp if cell blocks and microbiopsies are obtained as well.

Radiologist input and skill; more precise guided sampling of the various areas would be ideal.

my suggestion not listed... - but maybe i didnt' send it? very bad upper respiratory ick the last week and my brain isn't working too well.

my thought: their position is totally based on the Radiology position of HCC being diagnosable by radiologists. But there are no radiologists as co-authors with them. Maybe "our" radiologists can write a comment on their response, indicating the caveats from the radiologic perspective. OR, maybe even better, have alex get the LI-RADs group to respond with a more nuanced use of the radiologic contributions...?

just a thought i don't want to get lost in the shuffle... sorry if i didnt' actually transmit it before

Peter & Mike, congrats on the Editorial, really a great accomplishment!

Apologies for this delayed response, but I’ve done some surveying among our clinicians to check what the practice is and what the thoughts are on “biopsy-ing HCC”.

The practice:Imaging is central; a biopsy is only considered when imaging is inconclusiveFor patients on the LT waiting list Eurotransplant requires 2 diagnostic modalities to confirm the dx of HCC if a candidate wants to climb on the waiting list – so here’s also a chance that a biopsy will be done.

The thinking:- There is still a deep rooted believe of needle track seeding.- At the same time there is growing awareness of the necessity to have tissue for the (near) future. Recently a Dutch multidisciplinary and multicenter working group on HCC has been established that definitely underlines the importance of tissue harvesting and biobanking.

So all in all, while realizing that NL has only a modest burden of HCC I think that there is certainly hope for a change of attitude. The hardest hurdle is the well-established practice in which the BCLC/EASL/AASLD algorithm is ingrained and doctors are convinced they can treat without a biopsy. At this point Hala made a point we should consider, what therapeutical consequences can there be when we are able to subtype the tumor?Should we invite an HCC-oncologist to clarify the necessity of a bx from their point of view?

I think it is also a good idea to invite a radiologist as Neil suggested, since their role is so central and the yes/no biopsy decision currently depends on their certainties. To have the radiologist’s (nuanced) point of view to go along with us as a diagnostic team like in other solid tumors would strengthen our case.

The ideas of collaborative studies are great and I will be happy to add cases. If possible we may also add the number of bleeding/seeding data along with the biopsy cases.

Aileen’s remark on cytology is another point that we could discuss. Do many of us deal with FNAB on HCC? I saw the Beaujon’s paper (J Hepatol 2014, 61:589) and thought could FNAB be an alternative for the regular biopsies?

On my side, I went back to our files and, although our clinicians mention they follow the algorithm from the excellent group of Barcelona Clinic, we do havenot so few biopsies ( I am now going back to see how much tissue we still have in the blocks to bring up the number of pairs I have).

From this initial revisit of my cases, some reasons for the clinicians to biopsy are :

3. TACE or Radiofrequency (previously, ethanol ablation) raise specific questions, both regarding to prediction of response and morphological changes induced by these procedures

If as many of us can put these pairs together, we could select some of these questions for one or more studies validated in the surgical specimens (ressections or Tx) approaching diagnostic criteria , prognostic and predictive markers, as well as assessing heterogeneity (in cases which went straight for surgery OR due to changes induced by "bridge therapies")

Very handy. Adds another perspective. Hopefully by June we' ll get paired cases.

The surgeons are planning to do one core biopsy of HCC (not necessarily atypical cases) to assess grading for expanded criteria selection of patients for LTx.I pointed out the possible likelihood of missing the worse area with only one core biopsy. They are not keen to procure > one sample with FNA technique.

But at least they are intending to biopsy selected patients. Good to see the sampling accuracy when the explants arrive. Hope to get some cases by June.